The Synthesis And Application Of PEG Block Copolymer Micelles As Drug Carrier

Block copolymer micelles as drug carrier is an effective method. Although thismethod has made great process in vitro experiments and animal experiments, but ithas some problem in clinical case. anti-cancer drug undesired release at non-targetssites and preferential accumulation is not enough at tumor tissues in the process ofblood circulation. There are two methods could prevent loaded drug releaseprematurely:(1)To improve micelles stability and (2)to enhance hydrophobic blockinteraction with anti-cancer drug. External stimulus could resolve drug release fromcore of micelles. This external stimulus make micelles out of stability to improve theselectivity and efficiency of drug delivery to desired sites.To resolve drug release prematurely and preferential accumulation under-dose attumor tissues, we designed the micelle of PEG-P(AGE-co-MSA) chelate withcis-platinum. The cis-platinum as the core of micelle, chelate with the carboxyl groupof PEG-P(AGE-co-MSA). PEG is hydrophilic block of micelle, it could preventprotein from absorption and cell adhesion. The preferential accumulation ofchemotherapeutic agents in solid tumors as a result of the enhanced vascularpermeability of tumor tissues compared with healthy tissue. The pH at normalphysiological environment is7.4,while the pH is5.5-6.5at tumor tissues. The pHsensitive block copolymer micelle will destroy promptly and release anti-cancer drugimmediately.This paper according to the method of anionic polymerization, micromoleculepotassium2-(2-Methoxyethoxy)ethanolate as initiator, then change the method ofinject monomers to synthesize PEG-PAGE、poly(EO-co-AGE)、Poly(EO-co-Gly)three block copolymer. PEG-PAGE and poly(EO-co-AGE) modify the end of chain tochange allyl to carboxyl. Poly(EO-co-Gly) modify by esterification obtain carboxyl.Three block copolymer chelate with cis-platinum and then self-assemble micelle.There are characterized by dynamic light scattering(DLS),Zeta potential, Inductively Coupled Plasma Optical Spectrometer(ICP-OES),Transmission ElectronMicroscope (TEM) et al. The micelle of PEG-P(AGE-co-MSA) compare with themicelle of Poly(EO-co-Gly)-DA is more stability. Block copolymerPEG-P(AGE-co-MSA) could chelate with more cis-platinum and the size is about100nm-200nm，the drug loading capacity is reach up to33.3%.When the pH isdescend to5.5,50hours later,about56.64%cis-platinum get released from micelle ofPEG-P(AGE-co-MSA)...